Receptor-mediated and lectin-like activities of carp (Cyprinus carpio) TNF-alpha.

TitleReceptor-mediated and lectin-like activities of carp (Cyprinus carpio) TNF-alpha.
Publication TypeJournal Article
Year of Publication2009
AuthorsForlenza, M., S. Magez, J. P. Scharsack, A. Westphal, H. F. J. Savelkoul, and G. F. Wiegertjes
JournalJ Immunol
Date Published2009 Oct 15
KeywordsAmino Acid Sequence, Animals, Carps, Cell Movement, Endothelial Cells, Fish Diseases, Gene Expression, Lectins, Molecular Sequence Data, Pentoxifylline, Phagocytes, Phagocytosis, Phosphodiesterase Inhibitors, Recombinant Proteins, Sequence Alignment, Trypanosomiasis, Tumor Necrosis Factor-alpha, Up-Regulation

Functional characterization of TNF-alpha in species other than mammalian vertebrates is limited, and TNF-alpha has been studied in a limited number of fish species, primarily in vitro using recombinant proteins. Studies on TNF-alpha from different fish species so far pointed to several inconsistencies, in particular with respect to some receptor-mediated activities of fish TNF-alpha, such as the ability to directly activate phagocytes. In the present study a comprehensive analysis of in vitro as well as in vivo biological activities of two isoforms of carp TNF-alpha was performed. Our results show that carp TNF-alpha directly primes carp phagocytes and indirectly promotes typical receptor-mediated activities such as phagocyte activation by acting via endothelial cells. Additionally, for the first time in nonmammalian vertebrate species, the lectin-like activity of fish TNF-alpha homologs was investigated. Our results show an evolutionary conservation of function of this receptor-independent activity of TNF-alpha not only in cyprinid fish, but also in perciform and salmonid fish. The role of TNF-alpha in vivo, during infections of carp with the blood parasite Trypanoplasma borreli, was examined using three fundamentally different but complementary approaches: (1) inhibition of TNF-alpha expression, (2) overexpression of TNF-alpha, and (3) inhibition of shedding of membrane-bound TNF-alpha. Our results show that, also in fish, a tight regulation of TNF-alpha expression is important, since depletion or excess of TNF-alpha can make an important difference to survival of infection. Finally, we demonstrate a crucial protective role for membrane-bound TNF-alpha, which has a yet unexploited function in fish.

Alternate JournalJ. Immunol.
PubMed ID19786556